Regulation of nestin expression by thrombin and cell density in cultures of bone mesenchymal stem cells and radial glial cells

• Published in: BMC neuroscience Vol. 8; no. 1; p. 104
• Main Authors: Wautier, Franz, Wislet-Gendebien, Sabine, Chanas, Grazyna, Rogister, Bernard, Leprince, Pierre
• Format: Journal Article Web Resource
• Language: English
• Published: England BioMed Central Ltd 30.11.2007; BioMed Central; BMC
• Subjects: Animals; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Blood Proteins - pharmacology; Bone Marrow Cells - cytology; Care and treatment; Cell Count; Cell Differentiation - drug effects; Cell Division - drug effects; Cells, Cultured; Cellular therapy; Central nervous system diseases; Gene Expression - drug effects; Intermediate Filament Proteins - genetics; Intermediate Filament Proteins - metabolism; Intermediate Filament Proteins/genetics/metabolism; Life sciences; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - physiology; Mesenchymal Stem Cells/cytology/drug effects/physiology; Mice; Mice, Inbred Strains; Mitogens - pharmacology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins/genetics/metabolism; Nestin; Neuroglia - cytology; Neuroglia - drug effects; Neuroglia - physiology; Neuroglia/cytology/drug effects/physiology; Phenotype; Rats; Sciences du vivant; Stem cells; Thrombin - pharmacology; Belgium
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/1471-2202-8-104

Bone marrow stromal cells and radial glia are two stem cell types with neural phenotypic plasticity. Bone marrow mesenchymal stem cells can differentiate into osteocytes, chondrocytes and adipocytes, but can also differentiate into non-mesenchymal cell, i.e. neural cells in appropriate in vivo and in vitro experimental conditions. Likewise, radial glial cells are the progenitors of many neurons in the developing cortex, but can also generate astrocytes. Both cell types express nestin, an intermediate filament protein which is the hallmark of neural precursors. In this study, we demonstrate that thrombin, a multifunctional serine protease, stimulates the growth of radial glial cells (RG) and mesenchymal stem cells (MSCs) in a dose-dependent manner. In RG, the mitogenic effect of thrombin is correlated with increased expression of nestin but in MSCs, this mitogenic effect is associated with nestin down-regulation. Both cell types express the PAR-1 type receptor for Thrombin and the effect of Thrombin on both cell types can be mimicked by its analogue TRAP-6 activating specifically this receptor subtype or by serum which contains various amount of thrombin. Moreover, we also demonstrate that serum deprivation-induced expression of nestin in MSCs is inhibited by high cell density (> 50,000 cells/cm2). This work shows that thrombin stimulates the growth of both RG and MSCs and that nestin expression by MSCs and RG is regulated in opposite manner by thrombin in vitro. Thrombin effect is thus associated in both cell types with a proliferating, undifferentiated state but in RG this involves the induction of nestin expression, a marker of immaturity for neural progenitors. In MSCs however, nestin expression, as it corresponds to a progression from the mesenchymal "undifferentiated", proliferating phenotype toward acquisition of a neural fate, is inhibited by the mitogenic signal.